The present invention relates generally to man-made apparatus that substitutes for natural kidney function, and more particularly to a compact, easy-to-use hemofiltration system in which ultrafiltrate is purified via reverse osmosis to create pure water, and infusate concentrate is combined with the purified ultrafiltrate to create infusate.
Loss of human renal function, for example due to kidney disease, affects hundreds of thousands of people worldwide. In the past, chronic renal failure has meant almost certain death. More recently, renal failure is treatable by kidney transplant and/or less-physiologically traumatic procedures such as hemodialysis, hemofiltration or peritoneal dialysis (dialysis therapy). Existing hemodialysis and hemofiltration systems operate by withdrawing blood from a patient, treating the blood to remove waste, and re-introducing treated blood into the patient. Hemodialysis operates by bringing blood into contact with one side of a semipermeable membrane while a dialysis solution (dialysate) is brought into contact with the other side of the membrane. Uremic toxins diffuse out of the blood, through the semipermeable membrane due to a concentration gradient across the membrane, and into the dialysate. Hemofiltration operates by passing the blood through a filter to remove elements smaller than the filter pore size and replacing with a physiologic solution free of toxins (infusate).
The prior art contains examples of blood treatment devices that make use of combinations of multiple dialyzers, multiple filters, or combinations of filter and dialyzer. Kraus, et al., in xe2x80x9cUrea-Rejecting Membranes and Their Application in the Development of a Miniature Artificial Kidneyxe2x80x9d, J Memb. Sci., 1, 115-127, 1976 describe a system for continuous regeneration of peritoneal dialysate water. A dialysis unit is provided for purifying peritoneal dialysis solution, and a filter continuously purifying dialysate provided to the dialysis unit.
Ghezzi, et al. (U.S. Pat. No. 5,194,157) describe a blood purification system including, in series, a hemofiltration element followed by a hemodialysis element. Blood from a patient is first filtered in the hemofiltration element, then passed through the hemodialysis element and returned to the bloodstream. Ultrafiltrate from the hemofiltration element can be regenerated by being passed through a second filter and introduced into the flow of blood between the hemofiltration element and the hemodialysis element.
Gigou, et al. (U.S. Pat. No. 3,926,797) describe a separation system that can be used for blood purification. The system includes an ultrafiltration cell that receives blood from a patient, filters the blood, and returns the filtered blood to the patient. The ultrafiltrate can be purified using a dialysis unit, the purified ultrafiltrate combined with filtered blood for re-introduction into the patient. A device such as an active charcoal column or an ion exchange resin column can be used to remove waste from the dialysate of the dialyzer.
Brown (U.S. Pat. No. 3,579,441) described a blood purification unit including an ultrafilter for filtering blood from a patient and returning filtered blood to the patient. The ultrafiltrate can be passed through a hyperfilter, the hyperfiltrate being combined with purified blood for re-introduction into the patient. A reservoir is provided for introduction of make-up electrolyte into the hyperfiltrate for re-combination with the filtered blood. While the above-noted and other systems represent, in many cases, useful contributions to the art, many systems include inherent drawbacks. Hemodialysis, in general, is more expensive, more complex, and more difficult to employ than is hemofiltration. Specifically, where a dialysis unit is used to remove waste from a physiological fluid stream and the stream is being re-introduced into a patient, a relatively large volume of dialysate typically is required to create a continuous passage against the side of the dialyzer semipermeable membrane opposite the side addressed physiological fluid. Since the dialysate must be pure to the extent that it is free of chlorine, fluorine, and other poisonous ions that can cross a semipermeable membrane, significant effort is required to produce the necessary volume of purified water.
In many continuous hemofiltration systems ultrafiltrate waste must be replaced by infusate, which often is provided as a fluid for direct introduction into the patient, for example by being introduced into a conduit returning cleansed blood to a patient. In this instance pure, sterile infusate is required, adding complication and cost.
Most man-made renal function systems are not designed for convenient home use. In general, artificial renal treatment is given in a clinical outpatient setting for reasons of safety, since factors such as fluid balance and equipment complexity are critical. Of course, loss of a threshold amount of blood results in death. However, since victims of renal failure treated by man-made renal function systems must spend a significant amount of time undergoing dialysis therapy, these patients must spend a significant amount of time out of their homes if treated in a clinical setting.
Accordingly, it is a general object of the present invention to provide a blood treatment system which is simple to use that does not requires neither the generation of a large volume of pure dialysate solution, nor provision of a sterile replacement infusate formulation.
The invention includes, in one aspect, a method of purifying bloodstream waste, for the purpose of replacing kidney function, and in another aspect involves forming an infusate solution suitable for introduction into a patient from sterile or non-sterile infusate concentrates. In another aspect of the invention, a system or systems are provided for performing the above functions.
Specifically, in one aspect of the invention, a method is provided for purifying blood stream waste and forming a forming an infusate. Bloodstream waste from a patient is purified to form essentially pure water. A non-sterile infusate additive is sterilized to form a patient-sterile infusate additive, and the essentially pure water, derived from the patient""s blood stream waste, is combined with the patient-sterile additive to form an infusate solution suitable for introduction into the blood stream of the patient.
In some embodiments, the bloodstream waste is purified into essentially pure water by subjecting the bloodstream waste to reverse osmosis to remove uremic toxins, with or without a recycle loop. In another embodiment, the blood stream waste is purified by distillation or exposure to a sorbent. In some embodiments, the bloodstream waste is produced by continuously drawing blood from a patient and subjecting the blood to a purification step, such as hemofiltration, to separate the bloodstream waste from cleansed blood. In other embodiments, the bloodstream waste comprises peritoneal dialysate. In some embodiments of the experiment, the infusate solution is prepared by contacting the essentially pure water, derived from bloodstream waste, with a patient-sterile side of a semi-permeable membrane while simultaneously contacting a nonsterile additive with the opposite side of the membrane, thus allowing the additive to be sterilized while passing through the membrane to form the infusate solution. In certain embodiments of the invention, the infusate solution is combined with the cleansed blood and continuously reinfused into the patient.
Another aspect of the invention involves dialyzing a nonsterile infusate additive into a fluid across a semi-permeable membrane. Net ionic flow across the membrane into the fluid occurs thus creating an infusate solution suitable for introduction into a patient without further treatment.
Yet another aspect involves combining a fluid infusate output from a unit containing a semi-permeable membrane with fluid output from a blood purification device to form an infusate solution suitable for introduction into the bloodstream of a patient. In this aspect of the invention, net ionic flow can occur across the semi-permeable membrane and into the infusate. In some embodiments, a fluid, such as essentially pure water, passes through the semi-permeable membrane unit to form the fluid infusate output and no solutes are removed from the fluid.
The present invention also entails forming essentially pure, sterile water from essentially pure, nonsterile water by passing the nonsterile water through an ultrafiltration membrane. In this embodiment, the resulting essentially pure, sterile water is then added to an infusate concentrate to form an infusate solution. Impure blood is also passed through the ultrafiltration membrane to remove ultrafiltrate waste through the membrane and recover cleansed blood from the membrane.
The invention also includes a method for creating an infusate solution suitable for introduction into a patient by allowing a non-sterile infusate additive to diffuse across a semi-permeable membrane. The membrane separates a container into a non-sterile chamber, within which the infusate additive is contained, and a sterile chamber, containing sterile fluid.
Another aspect involves dialyzing an infusate additive is dialyzed into a fluid stream across a semi-permeable membrane. In this embodiment, a net ionic flow occurs across the semi-permeable membrane into the fluid stream to form an infusate solution which is introduced into the bloodstream of the patient.
The invention also entails passing a fluid stream through a semi-permeable membrane unit. Within the semi-permeable membrane unit, an infusate additive is added to the fluid stream, without removing any solutes from the fluid stream, to form an infusate solution suitable for introduction into a patient.
Another aspect of the invention involves maintaining a concentration gradient across a semi-permeable membrane in a semi-permeable membrane unit. Diffusion then occurs from a first side of the membrane to a second side. The concentration gradient is maintained and diffusion is enabled by feeding fluid with an elevated concentration from a constant volume fluid enclosure to the first side while removing from the first side fluid of a relatively lower concentration. The removed fluid is then returned to the constant volume fluid enclosure.
The invention provides a method of monitoring an infusate solution. The monitoring method involves dialyzing an infusate additive into a fluid stream and measuring the conductivity of the resultant infusate solution.
The invention also provides a method of purifying a solution. The method involves contacting an unpurified fluid stream with a first side of a filter where the stream is divided into two streams. The first stream passes through the filter, and the second stream does not. The second stream is recirculated to the first side of the filter through a recirculation conduit including a receptacle with a variable volume. A portion of the second stream is added to an expandable bag and a constant amount is recirculated to the first side of the filter and added back to the stream of unpurified fluid.
In one aspect of the invention, a method for fluid purification includes establishing a stream of fluid containing a species directed toward a filter having an upstream and a downstream side. A first portion of the stream of fluid passes through the filter free of the species, and a second portion of the fluid, containing the species, is maintained on the upstream side of the filter. The second portion of the stream is diverted from the filter through a recirculation conduit which includes a variable volume receptacle. The second portion of the stream is recirculated and added to the stream of fluid directed toward the filter.
The invention also encompasses various novel apparatus and systems for performing the inventive methods. In one embodiment, a system is provided that includes a semi-permeable membrane unit, which includes a semi-permeable membrane having a patient-sterile and a nonsterile side. The system also includes a water purification unit that has an inlet for receiving impure water and an outlet for delivering purified water. The water purification unit is constructed and arranged to purify the water between the inlet and the outlet. Included also is a fluid conduit that connects the outlet of the water purification unit with the sterile side of the semi-permeable membrane unit. In certain embodiments, the water purification unit comprises a reverse osmosis unit. The system can also include a blood purification unit that receives impure blood from a patient, an separates the impure blood into a cleansed blood stream and a bloodstream waste stream that is deliverable to the water purification unit inlet. In particular embodiments, the blood purification device comprises a hemofilter.
The invention also encompasses systems comprising a semipermeable membrane unit, including a semi-permeable membrane having a patient-sterile side and a nonsterile side where the patient-sterile side is in fluid communication with a patient-sterile conduit that is connectable to a fluid system of the patient. The system also includes fluid circuitry associated with the semi-permeable membrane unit that is constructed and arranged to provide an osmotic pressure driving force that creates net ionic transport across the semi-permeable membrane from the nonsterile side to the patient-sterile side.
One aspect of the invention provides a system including a semi-permeable membrane having a patient-sterile side and a nonsterile side, and a blood purification device having a conduit that is fluidly connectable to the patient""s bloodstream for delivering cleared blood to the patient. The system further includes a fluid conduit that allows for connection between the patient-sterile side of the semi-permeable membrane and the fluid conduit of the blood purification device and fluid circuitry associated with the semi-permeable membrane unit that is constructed and arranged to provide osmotic pressure driving net ionic flow across the semi-permeable membrane from the nonsterile to the patient-sterile side.
In another aspect, the system includes a semi-permeable membrane, which has one side in fluid communication with an infusate concentrate, and is fluidly connectable with a bloodstream of a patient without the need to make or break conduit connections.
Another system, as provided by the invention, includes a semi-permeable membrane unit having a semi-permeable membrane with a first side and a second side. The first side is in fluid communication with a conduit that is connectable to a bloodstream of a patient. Also included is fluid circuitry associated with the semi-permeable membrane that is constructed and arranged to provide osmotic pressure to drive ionic transport across the semi-permeable membrane from a nonsterile to a patient sterile side.
Another system of the invention includes a semi-permeable membrane unit with a semi-permeable membrane that has a first side and a second side, the invention provides an enclosure that has an inlet and an outlet, with both the inlet and the outlet being fluidly connectable to the first side of the semi-permeable membrane. The enclosure further includes a movable, nonporous barrier within the enclosure that separates the inlet from the outlet.
Furthermore, the invention also encompasses systems including a semi-permeable membrane unit with a semi-permeable membrane that has a first side and a second side where the first side is surrounded by an enclosure. This enclosure includes an inlet, for receiving fluid for contact with the first side of the membrane, and an outlet for discharging fluid from the first side of the membrane. The inlet and the outlet of the enclosure are in fluid communication with a first and a second sealed fluid container respectively.
Articles are provided by the invention that include a impermeable container separated into two chambers by a semipermeable membrane. The first chamber, bounded on one side by one side of the semi-permeable membrane, is nonsterile. The second chamber, bounded on one side by the other side of the semi-permeable membrane is sterile. In certain embodiments, the chamber can contain a nonsterile infusate additive.
Other advantages, novel features, and objects of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings, which are schematic and which are not intended to be drawn to scale. In the figures, each identical or nearly identical component that is illustrated in various figures is represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention.